| First Author | Liu E | Year | 2021 |
| Journal | Front Cell Dev Biol | Volume | 9 |
| Pages | 710967 | PubMed ID | 34490261 |
| Mgi Jnum | J:310891 | Mgi Id | MGI:6762232 |
| Doi | 10.3389/fcell.2021.710967 | Citation | Liu E, et al. (2021) ZDHHC11 Positively Regulates NF-kappaB Activation by Enhancing TRAF6 Oligomerization. Front Cell Dev Biol 9:710967 |
| abstractText | Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a RING domain ubiquitin ligase that plays an important role in nuclear factor-kappaB (NF-kappaB) signaling by regulating activation of the TAK1 and IKK complexes. However, the molecular mechanisms that regulate TRAF6 E3 activity remain unclear. Here, we found that ZDHHC11, a member of the DHHC palmitoyl transferase family, functions as a positive modulator in NF-kappaB signaling. ZDHHC11 overexpression activated NF-kappaB, whereas ZDHHC11 deficiency impaired NF-kappaB activity stimulated by IL-1beta, LPS, and DNA virus infection. Furthermore, Zdhhc11 knockout mice had a lower level of serum IL6 upon treatment with LPS and D-galactosamine or HSV-1 infection than control mice. Mechanistically, ZDHHC11 interacted with TRAF6 and then enhanced TRAF6 oligomerization, which increased E3 activity of TRAF6 for synthesis of K63-linked ubiquitination chains. Collectively, our study indicates that ZDHHC11 positively regulates NF-kappaB signaling by promoting TRAF6 oligomerization and ligase activity, subsequently activating TAK1 and IKK complexes. |
